Can vitamin C supplementation cause hyperuricemia, especially at doses >1 g per day or in patients with gout, hyperuricemia, chronic kidney disease, or diuretic use?

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Vitamin C Does Not Cause Hyperuricemia

Vitamin C supplementation does not cause hyperuricemia; in fact, it modestly lowers serum uric acid levels, though the effect is clinically insignificant in patients with established gout. 1, 2

Evidence from Major Guidelines

The 2020 American College of Rheumatology guideline conditionally recommends against adding vitamin C supplementation for patients with gout, not because it raises uric acid, but because the urate-lowering effect is too small to be clinically meaningful 1. Two small RCTs (n=29 and n=40) in gout patients showed that vitamin C produced clinically insignificant changes in serum urate concentrations 1.

The 2017 American College of Physicians guideline noted that vitamin C supplementation reduced serum urate levels by −20.8 µmol/L (−0.35 mg/dL), though this was based on low-quality evidence with high heterogeneity 1.

Direction of Effect: Vitamin C Lowers Uric Acid

Multiple lines of evidence demonstrate that vitamin C has a urate-lowering, not urate-raising, effect:

  • Population studies show inverse associations: Higher total vitamin C intake (dietary plus supplemental) is associated with lower odds of hyperuricemia, with multivariate-adjusted odds ratios of 0.66 (95% CI 0.58-0.76) for the highest versus lowest quartile of intake in US adults 3. Similar inverse associations were found in Korean populations 4.

  • Dose-response relationship: In men without hypertension, adjusted mean uric acid concentrations decreased progressively across vitamin C intake categories from 6.4 mg/dL (<90 mg/day) to 5.7 mg/dL (≥1000 mg/day), with a plateau effect above 400-500 mg/day 5.

  • Mechanistic data: Animal studies demonstrate that vitamin C at 10 mg/kg/day reduced serum uric acid by 20% and xanthine oxidase activity by 20% in hyperuricemic rats, while also reducing inflammation and fibrosis 6.

Clinical Trial Evidence in Gout Patients

The most relevant study for your question is a 2013 pilot RCT in 40 patients with established gout 2:

  • Vitamin C 500 mg/day for 8 weeks produced a mean reduction of only 0.014 mmoles/L (0.23 mg/dL) in serum urate
  • This was significantly less than allopurinol, which reduced urate by 0.118 mmoles/L (1.9 mg/dL)
  • The effect was deemed clinically insignificant despite increased plasma ascorbate levels
  • 30% of vitamin C recipients and 25% of controls were on diuretics, showing no adverse interaction

Important Caveats and Context

The ACR recommendation against vitamin C is based on insufficient benefit, not on harm 1. The guideline explicitly states that "data on vitamin C were insufficient to support continued recommendation for its use" because the effect size is too small to justify routine supplementation in gout management 1.

Vitamin C at high doses (≥1000 mg twice daily) can theoretically increase urinary oxalate excretion by 22%, which is relevant for calcium oxalate kidney stone formers with hyperoxaluria 1. However, this relates to kidney stone risk, not hyperuricemia. The Kidney International guideline recommends that calcium stone formers with hyperoxaluria discontinue vitamin C supplements, but does not restrict dietary vitamin C from foods 1.

There is no evidence that vitamin C causes hyperuricemia in patients with chronic kidney disease, diuretic use, or any other population 2, 3, 4. The concern about vitamin C in these contexts relates to oxalate metabolism and kidney stones, not uric acid elevation.

Bottom Line for Clinical Practice

  • Vitamin C does not cause hyperuricemia at any dose studied (up to ≥1000 mg/day) 5, 3
  • The modest urate-lowering effect (0.2-0.4 mg/dL) is too small to be therapeutically useful in gout patients who require pharmacologic urate-lowering therapy to achieve target serum urate <6 mg/dL 1, 2
  • Do not discontinue vitamin C if a patient is taking it for other appropriate indications (e.g., immune support, antioxidant purposes) 1
  • The only population that should avoid high-dose vitamin C supplements (≥1000 mg/day) is calcium oxalate stone formers with hyperoxaluria, due to increased urinary oxalate, not uric acid concerns 1

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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